Zinc Finger CCCH-Type Antiviral Protein 1 Restricts the Viral Replication by Positively Regulating Type I Interferon Response.

Baoge Zhang,Ji-Long Chen,Na Chen,Lifeng Xu,Mohsan Ullah Goraya,Yan Hong,Meiyi Zhu

doi:10.3389/fmicb.2020.01912

Abstract

Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1) is a host antiviral factor that can repress translation and promote degradation of specific viral mRNAs. In this study, we found that expression of ZC3HAV1 was significantly induced by infection with influenza A virus (IAV) and Sendai virus (Sev). It was shown that deficiency of IFNAR resulted in a dramatic decrease in the virus-induced expression of ZC3HAV1. Furthermore, transfection with poly(I:C) and treatment with interferon β (IFN-β) induced the ZC3HAV1 expression. Interference with the endogenous expression of ZC3HAV1 enhanced the replication of influenza virus by impairing the production of IFN-β and MxA, following the infection of influenza virus. In contrast, ectopic expression of ZC3HAV1 significantly restricted the replication of influenza virus by increasing the IFN-β expression. In addition, ZC3HAV1 also promoted the induction of tumor necrosis factor and interleukin 6. These results suggest that ZC3HAV1 is induced by IFN-β/IFNAR signaling during IAV and Sev infection and involved in positive regulation of IFN-dependent innate antiviral response.

Highlights

In response to viral infection, the host innate immune system is rapidly induced to restrict the viral replication and spread
Mice were infected with WSN/33 virus (WSN) for 48 h, and the lung tissues were collected, and total RNA was isolated. These samples were examined by quantitative RT-PCR (qRT-PCR), and the results showed that the expression levels of ZC3HAV1 in IFNAR knockout A549 cells and in lung tissues of IFNAR knockout mice were significantly lower than those in the control group after influenza virus infection (Figures 2A,B)
To identify the genes involved in the innate immune response to influenza A virus (IAV) infection, microarray analysis was performed for examining the alterations of gene expression in A549 cells infected with or without WSN virus

Summary

Introduction

In response to viral infection, the host innate immune system is rapidly induced to restrict the viral replication and spread. Innate immune responses are initiated by the recognition of non-selfligands expressed by pathogens, called pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors (PRRs) expressed on host cells. Toll-like receptors 3 and 7 (TLR3/7) in endosome recognize the foreign nucleic acid and proteins internalized via endocytosis from the extracellular space. Cytosolic retinoic acidinducible gene (RIG) like receptors (RLRs) and NOD like-receptors detect PAMPs in the infected cells. Viral RNA and DNA are major PAMPs sensed by the PRRs that trigger the innate immunity against viral infection. Viral RNA can be recognized by endosomal TLRs and cytosolic RIG-I-like receptors (Fensterl et al, 2015). Stimulation of PRRs can activate the transcription factors NF-κB

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Results

Conclusion